Ischaemia and reperfusion injury of rat liver increases expression of glutathione S-transferase A1/A2 in zone 3 of the hepatic lobule.
Effects of ischaemia-reperfusion injury (I/R) of liver on expression of rat glutathione S-transferase (rGST) isoenzymes that metabolize products of oxidative stress were examined. Rats underwent lobar liver ischaemia for 30 min followed by reperfusion. In ischaemic lobes, rGSTA1/A2 transcript levels increased significantly 12 h after I/R (2.94-fold) and protein levels increased significantly at 24 h (1.45-fold); increased transcript levels were also observed in nonischaemic lobes (1.78-fold). Superoxide dismutase prevented I/R and the increases in transcript and protein levels in ischaemic and non-ischaemic lobes. By in-situ hybridization, increases in transcript levels at 6 h were present in zones 2 and 3 of the ischaemic lobes and peaked at 12 h (2.5-fold zone 2, 4.5-fold zone 3). Significant increases in transcript levels also were observed at 24 h in zones 2 (2.0-fold) and 3 (2.9-fold) of non-ischaemic lobes. Nuclear run-off assays showed a 1.8-fold increase in rGSTA1/A2 transcription rates in ischaemic lobes at 3 h. We conclude that I/R causes increased rGSTA1/A2 expression in the zone of the hepatic lobule most susceptible to oxidative injury and that this expression may be an important defence against injury.
Branum
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Department of Surgery, Emory University School of Medicine, 2101 Woodruff Memorial Building, 1639 Pierce Drive, Atlanta, GA 30322, USA.
Selim
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N
Liu
X
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Whalen
R
R
Boyer
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TD
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005982:Glutathione Transferase / Q000378:metabolism*; D017403:In Situ Hybridization; D007511:Ischemia / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D007527:Isoenzymes; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D010634:Phenobarbital